YIF1B-related Kaya-Barakat-Masson Syndrome: Report of a new patient and literature review.

ABSTRACT

Kaya-Barakat-Masson syndrome (KABAMAS) is a recently identified severe neurodevelopmental disorder characterized by severe global developmental delay, epilepsy, movement disorder, epilepsy, and microcephaly. KABAMAS is caused by bi-allelic variants in the YIF1B gene which encodes a trafficking protein involved in the anterograde traffic from the endoplasmic reticulum to the cell membrane including neural cells in association with other trafficking proteins and also Golgi apparatus morphology. That's why clinical overlapping between KABAMAS and golgipathies isn't surprising. It is a rare condition with only 24 patients reported to date. Here we described a 5.5-year-old boy presenting with severe global developmental delay, epileptic encephalopathy, microcephaly, dystonia, spasticity, blindness, feeding difficulties, respiratory failure, and dysmorphic features. Whole exome sequencing identified homozygous splice site variation (NM_001039672.3 c.297+1G > A) in the YIF1B gene. This splice site variant is rare in the general population (gnomAD Variant allele fraction (VAF) 0.0007%, 2 heterozygotes, 0 homozygotes) and has not previously been associated with the disease. Multiple in silico tools predict a deleterious effect of this splice site change. Considering the points mentioned above, we have considered the detected variant as pathogenic according to guidelines in light of current knowledge. By reporting a new case with the homozygous YIF1B splice site variant we provide further evidence to clinical and molecular data of this recently recognized severe neurodevelopmental disorder. We further emphasize that trafficking errors should be considered as an underlying mechanism in undiagnosed severe neurodevelopmental disorders.